Over the past decade, genome-scale molecular profiling of large childhood cancer survivorship cohorts has led to unprecedented advances in our understanding of the genetic and epigenetic bases of therapy-related adverse health outcomes in this vulnerable population. To facilitate the integration of knowledge generated from these studies into formulating next-generation precision care for survivors of childhood cancer, we summarize key findings of genetic and epigenetic association studies of long-term therapy-related adverse effects including subsequent neoplasms and cardiomyopathies among others. We also discuss therapy-related genotoxicities including clonal haematopoiesis and DNA methylation, which may underlie accelerated molecular ageing. Finally, we highlight enhanced risk prediction models for survivors of childhood cancer that incorporate both genetic factors and treatment exposures, aiming to achieve enhanced accuracy in predicting risks for this population. These new insights will hopefully inspire future studies that harness both expanding omics resources and evolving data science methodology to accelerate the translation of precision medicine for survivors of childhood cancer.

在过去的十年中，大型儿童癌症幸存者队列的基因组规模分子分析导致我们对这一弱势群体中与治疗相关的不良健康结果的遗传和表观遗传基础的理解取得了前所未有的进展。为了促进将这些研究产生的知识整合到为儿童癌症幸存者制定下一代精准护理中，我们总结了长期治疗相关不良反应的遗传和表观遗传关联研究的主要发现，包括随后的肿瘤和心肌病等。我们还讨论了与治疗相关的遗传毒性，包括克隆造血和 DNA 甲基化，这可能是分子加速衰老的基础。最后，我们重点介绍了针对儿童癌症幸存者的增强风险预测模型，该模型结合了遗传因素和治疗暴露，旨在提高预测该人群风险的准确性。这些新见解有望激发未来的研究，这些研究利用不断扩大的组学资源和不断发展的数据科学方法，以加速儿童癌症幸存者精准医学的转化。